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Circular RNA PVT1 silencing prevents ischemia-reperfusion injury in rat by targeting microRNA-125b and microRNA-200a
Journal of Molecular and Cellular Cardiology ( IF 5 ) Pub Date : 2021-06-05 , DOI: 10.1016/j.yjmcc.2021.05.019
Cheng Luo 1 , Guo-Xing Ling 1 , Bin-Feng Lei 1 , Xu Feng 1 , Xiao-Yong Xie 1 , Chen Fang 1 , Yu-Gui Li 1 , Xiong-Wei Cai 1 , Bao-Shi Zheng 1
Affiliation  

Circular RNAs (circRNAs) are essential regulators associated with many cardiac conditions, including myocardial infarction (MI). This study aimed to explore circRNA expression during MI development in an animal model and in hypoxia/reoxygenation (H/R)-treated cardiomyocytes. Microarray and real-time quantitative PCR showed that the circRNA PVT1 (circPVT1) was expressed at high levels in MI tissues and H/R-triggered cardiomyocytes. Loss-of-function assays were utilized for examining the influence of circPVT1 on cardiac function and cardiomyocyte properties. Cardiac function was measured by echocardiography at 7 d after MI. Reduced circPVT1 expression significantly decreased MI-triggered myocardial infarct size by 60% and prevented MI-triggered reductions in fractional shortening (%FS) and ejection fraction (EF%). Results of LDH, CCK-8, EdU staining, colony formation assays, and flow cytometry showed that circPVT1 silencing restored cell viability and proliferation while decreased apoptosis. Mechanistic experiments indicated that microRNAs (miR)-125b and miR-200a associated with circPVT1. We demonstrated that circPVT1 functioned as a competitive endogenous RNA (ceRNA) to sponge both miR-125b and miR-200a. Gain-of-function assays showed that miR-125b and miR-200a upregulation partially eliminated the effects of circPVT1 on cardiomyocyte properties. In addition, we found that the previously reported p53/TRAF6, SIRT7, Keap1/Nrf2, and PDCD4 pathways were regulated by the circPVT1/miR-125b/miR-200a axis. In conclusion, our study suggests that circPVT1 protects the myocardium from MI and H/R injury by preventing miR-125b- and miR-200a-mediated apoptotic signaling.



中文翻译:

环状 RNA PVT1 沉默通过靶向 microRNA-125b 和 microRNA-200a 预防大鼠缺血再灌注损伤

环状 RNA (circRNA) 是与包括心肌梗塞 (MI) 在内的许多心脏疾病相关的重要调节因子。本研究旨在探索动物模型和缺氧/复氧 (H/R) 处理的心肌细胞中 MI 发展过程中 circRNA 的表达。微阵列和实时定量 PCR 显示 circRNA PVT1 (circPVT1) 在 MI 组织和 H/R 触发的心肌细胞中高水平表达。功能丧失测定法用于检查 circPVT1 对心脏功能和心肌细胞特性的影响。在 MI 后 7 天通过超声心动图测量心脏功能。降低 circPVT1 表达可显着降低 MI 引发的心肌梗死面积 60%,并防止 MI 引发的缩短分数 (%FS) 和射血分数 (EF%) 降低。LDH、CCK-8、EdU 染色结果,集落形成测定和流式细胞术表明,circPVT1 沉默恢复了细胞活力和增殖,同时减少了细胞凋亡。机制实验表明,microRNAs (miR)-125b 和 miR-200a 与 circPVT1 相关。我们证明了 circPVT1 作为一种竞争性内源性 RNA (ceRNA) 可以吸收 miR-125b 和 miR-200a。功能增益测定表明,miR-125b 和 miR-200a 上调部分消除了 circPVT1 对心肌细胞特性的影响。此外,我们发现先前报道的 p53/TRAF6、SIRT7、Keap1/Nrf2 和 PDCD4 通路受 circPVT1/miR-125b/miR-200a 轴的调节。总之,我们的研究表明,circPVT1 通过阻止 miR-125b 和 miR-200a 介导的凋亡信号传导来保护心肌免受 MI 和 H/R 损伤。和流式细胞术表明,circPVT1 沉默恢复了细胞活力和增殖,同时减少了细胞凋亡。机制实验表明,microRNAs (miR)-125b 和 miR-200a 与 circPVT1 相关。我们证明了 circPVT1 作为一种竞争性内源性 RNA (ceRNA) 可以吸收 miR-125b 和 miR-200a。功能增益测定表明,miR-125b 和 miR-200a 上调部分消除了 circPVT1 对心肌细胞特性的影响。此外,我们发现先前报道的 p53/TRAF6、SIRT7、Keap1/Nrf2 和 PDCD4 通路受 circPVT1/miR-125b/miR-200a 轴的调节。总之,我们的研究表明,circPVT1 通过阻止 miR-125b 和 miR-200a 介导的凋亡信号传导来保护心肌免受 MI 和 H/R 损伤。和流式细胞术表明,circPVT1 沉默恢复了细胞活力和增殖,同时减少了细胞凋亡。机制实验表明,microRNAs (miR)-125b 和 miR-200a 与 circPVT1 相关。我们证明了 circPVT1 作为一种竞争性内源性 RNA (ceRNA) 可以吸收 miR-125b 和 miR-200a。功能增益测定表明,miR-125b 和 miR-200a 上调部分消除了 circPVT1 对心肌细胞特性的影响。此外,我们发现先前报道的 p53/TRAF6、SIRT7、Keap1/Nrf2 和 PDCD4 通路受 circPVT1/miR-125b/miR-200a 轴的调节。总之,我们的研究表明,circPVT1 通过阻止 miR-125b 和 miR-200a 介导的凋亡信号传导来保护心肌免受 MI 和 H/R 损伤。

更新日期:2021-06-23
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